Biomedical subjects
Publications and source records attributed to W J Oakes.
The Chiari II malformation and associated hydrosyringomyelia represent a complex spectrum of anatomic changes and clinical presentations whose management is rapidly changing as more is discovered about the natural history of these patients. Trends toward earlier operation on milder symptoms in selected patients may lead to improved neurologic outcome in these patients.
A 16-year-old white male presented with multiple abnormal extraocular movements secondary to an enhancing pineal tumor. Subtotal resection of the lesion revealed a mixed malignant germ cell tumor. The preoperative serum alpha-fetoprotein (AFP) was markedly elevated at 155 IU/L. The patient subsequently received radiotherapy and adjuvant chemotherapy consisting of cisplatin rotating monthly with vincristine and cyclophosphamide, with dramatic tumor regression and return of AFP to normal. Eighteen months later the persistence of a substantial tumor mass despite a normal AFP raised concern for residual active tumor. Histological examination of the resected lesion revealed benign teratoma and fibrous tissue. Repeat management of mixed malignant germ cell tumors, which demonstrate a persistent mass following an initial response to treatment.
Trilateral retinoblastoma, the intracranial malignancy associated with bilateral retinoblastoma, is an uncommon and clinically aggressive malignancy with a uniformly fatal outcome. Three children with newly diagnosed trilateral retinoblastoma were treated with systemic (cyclophosphamide and vincristine) and intrathecal (methotrexate, hydrocortisone, and cytarabine) chemotherapy, as well as craniospinal irradiation (one patient) in addition to therapy of the eye lesions. All three patients have had partial or complete response of the pineal tumors to chemotherapy, with no active disease eight or more years, 33 or more months, and 12 or more months, respectively, after diagnosis of the lesions.
Myelosuppression is a common sequelae of radiotherapy, occasionally delaying the completion of treatment. In this report, we describe successful reversal of radiation-induced neutropenia in a child receiving craniospinal irradiation by granulocyte colony-stimulating factor (G-CSF). We suggest that G-CSF be considered as supportive care in patients in whom neutropenia develops during radiotherapy.
Twenty-two pediatric patients with known CNS neoplasms underwent magnetic resonance (MR) imaging before and after intravenous injection of 0.1 mmol/kg gadoteridol injection as part of a Phase IIIB open label multicenter clinical trial. Intravenous administration of this neutral, nonionic contrast agent was found to be safe in children. No clinically relevant changes in vital signs or laboratory values (including complete blood count, blood chemistry, serum electrolytes, thyroid and metabolic panel and clotting function) were attributed to the administration of gadoteridol injection. There were no systemic complaints. The imaging characteristics of gadoteridol in pediatric CNS disease appeared similar to those of gadopentetate dimeglumine. Contrast enhancement was present in 17 of 22 patients (77%). The administration of gadoteridol injection provided additional clinically relevant information including improved visualization and delineation of the primary lesion, detection of additional lesions, determination of tumor recurrence and narrowing the list of differential considerations in all 17 enhancing studies as well as in 2 of 5 studies without signal intensity enhancement. The very low toxicity, inherent to this nonionic low osmolal paramagnetic contrast formulation may allow administration of increased doses at increased infusion rates for an increased number of indications with improved sensitivity.
Explore the source record for details and available documents.
Perinatal spinal cord injury is a relatively uncommon, but a frequently misdiagnosed disorder. Often, the injury is not suspected and an erroneous diagnosis is made. We present five cases of perinatal spinal cord injury. In four, the referring physicians (including pediatric neurologists) misdiagnosed the condition. In view of these diagnostic difficulties, we review the clinical, radiographic and pathologic aspects of these injuries. Serious spinal injuries occasionally occur in the perinatal period. With improving medical care, many infants with less severe injuries are surviving the neonatal period. Therefore, the prompt recognition of neonatal spinal cord damage is essential and allows for optimal treatment of the injured child.
Explore the source record for details and available documents.
PURPOSE: The Pediatric Oncology Group (POG) conducted a randomized phase II study to evaluate the activity of carboplatin and iproplatin in children with progressive or recurrent brain tumors. PATIENTS AND METHODS: The study was designed to evaluate the activity of these agents and to compare the toxicities associated with their use. Treatment consisted of carboplatin 560 mg/m2 at 4-week intervals or iproplatin 270 mg/m2 at 3-week intervals. RESULTS: The major toxicity observed was myelosuppression, particularly thrombocytopenia, for both agents. Ototoxicity (grade 1 or 2) was seen in 2.5% of patients treated with carboplatin and 1.3% of patients treated with iproplatin. The majority of patients with low-grade astrocytic neoplasms treated with carboplatin (nine of 12 patients) or iproplatin (eight of 12 patients) demonstrated tumor response or prolonged stable disease that persisted off-therapy. The duration of stable disease produced by carboplatin was particularly striking, ranging from 2 months to 68 + months (median, 40 + months). Neither drug demonstrated appreciable activity in the treatment of medulloblastoma (two of 26 responses to carboplatin, one of 14 responses to iproplatin), ependymoma (two of 17 responses to carboplatin, none of seven responses to iproplatin), high-grade glioma (two of 19 responses to carboplatin, one of 14 responses to iproplatin), or brain-stem tumors (one of 23 responses to carboplatin, none of 14 responses to iproplatin). CONCLUSION: Carboplatin is active against low-grade gliomas. Further evaluation of the role of carboplatin in the preirradiation treatment of children with low-grade gliomas of the optic pathway is currently underway in a clinical trial.
The treatment and subsequent developmental progress of six children with dorsal third ventricular cysts are described. This cystic malformation has a radiological appearance which is superficially similar to that of the dorsal cyst of alobar holoprosencephaly, especially when the third ventricular cyst is large. Indeed, previous reports have identified this abnormality as a form of holoprosencephaly. However, careful study reveals that the dorsal third ventricular cyst is a distinct entity both developmentally and clinically. The six patients in this series were effectively treated with shunts, and their subsequent developmental progress was assessed by means of the Prescreening Developmental Questionnaire-Revised as well as the Bayley Scales of Infant Development. The nomenclature and differences between this entity and the holoprosencephalies are reviewed. The authors conclude that dorsal third ventricular cysts have a developmental and clinical course more similar to that of arachnoid cysts than to that of the holoprosencephalies.
With only about 1,500 new cases a year of pediatric brain tumors, as many cases as possible must be enrolled in ongoing multicenter trials if therapeutic advances are to continue. To date, such trials have identified chemotherapeutic agents active against medulloblastoma, demonstrated the benefits of surgical debulking or resection in patients with astrocytic tumors, and shown the usefulness of chemotherapy to delay radiotherapy in very young children with malignant brain tumors. New trials are exploring the uses of intrathecal administration of 4-hydroperoxycyclophosphamide and radiolabeled monoclonal antibodies in brain tumor patients with subarachnoid metastases. The authors describe the results of completed trials of these new therapies, give details on new regimens being tested in ongoing investigations at centers across the nation, and urge the continued referral of children with brain tumors to academic institutions.
Head injuries are the most common cause of disability and death in children. Identification of children who require specialized management following a head injury will reduce the associated morbidity and mortality. Thus, it is important to differentiate the child who can be safely observed and who will recover spontaneously from the child who will develop a progressive neurologic deficit from a treatable cause. A thorough history, a tailored neurologic examination and limited radiographic studies will assist the family physician in making this determination.
We treated three children with optic pathway gliomas who had progressive disease associated with metastatic spread to the leptomeninges. One patient had radiographic resolution of leptomeningeal disease after treatment with intravenous carmustine and oral mercaptopurine but died of progressive pulmonary fibrosis. The second patient was treated with intravenous thiotepa, and the leptomeningeal disease remained stable. The third patient was treated with intravenous vincristine sulfate, cyclophosphamide, cisplatin, and etoposide and had a significant size reduction of the leptomeningeal lesion. Although leptomeningeal dissemination is a seemingly rare event, it is important that all children with optic pathway gliomas be considered for this possibility, particularly after the onset of new, atypical neurologic symptoms.
Two patients with brain stem gliomas were treated with hyperfractionated radiation therapy (HFR) (7,020 and 7,560 cGy, respectively). Despite initial clinical improvement during irradiation, both patients demonstrated clinical deterioration approximately 3 weeks after completion of radiotherapy. Cranial magnetic resonance imaging (MRI) revealed a progressive increase in distribution of abnormal brain stem signal consistent with either tumor or edema. 18FDG positron emission tomography (PET) was obtained in one patient and demonstrated a hypermetabolic lesion at diagnosis and a hypometabolic lesion at the time of clinical deterioration postirradiation. Management with a tapering dose of dexamethasone alone resulted in marked clinical (both patients) and radiographic (one patient) improvement, allowing reduction or discontinuation of this medication. These results suggest that patients with brain stem tumors demonstrating clinical and radiographic evidence of progressive tumor shortly after completion of HFR should be initially managed conservatively with dexamethasone, since these findings may be manifestations of reversible radiation-related neurotoxicity.
The spread of primary central nervous system (CNS) neoplasms beyond the confines of the neuraxis is a relatively uncommon observation. Extraneural metastases involving bone are quite rare, and have been observed almost exclusively in cases of medulloblastoma, high-grade (III-IV) astrocytoma, and glioblastoma multiforme. To date there has been only one case reported of bone metastasis from a "well-differentiated" astrocytoma. We now report two cases of astrocytoma in children with diffuse osteoblastic metastases and a fulminant clinical course. These cases demonstrate that due to the potential morphologic heterogeneity of these neoplasms, an initial biopsy diagnosis of low-grade astrocytoma does not always imply a benign clinical course.
Medulloblastoma is the most common central nervous system malignancy of childhood, with approximately 350 new cases seen in the United States each year. Although the low incidence of this tumor, compared with adult neoplasms such as breast or colon carcinoma, has limited laboratory and clinical research, recent studies have greatly enhanced our understanding of the biology, phenotype, genotype, and therapy of medulloblastoma. Further efforts to integrate laboratory and clinical studies of this tumor may allow design of novel therapeutic approaches resulting in enhanced disease-free survival.
Recent reports have suggested an association between congenital anorectal anomalies and occult spinal dysraphism. Eighty-seven patients with anal agenesis have been treated at this institution over the last 14 years. Two of these patients had spinal cord anomalies recognized at birth (a myelomeningocele and a tethered spinal cord). Two additional patients presented with progressive neurologic deficits in early childhood and were each found to have a tethered spinal cord. To further assess the magnitude of this problem, we have used magnetic resonance imaging (MRI) of the spine to survey prospectively 23 infants with anal agenesis. Twenty-one former patients who were asymptomatic were recalled and also studied. Four of 44 patients (9%) were found to have significant occult spinal dysraphism; each child had undergone neurosurgical operation without morbidity. MRI found each child to have a tethered spinal cord, either as an isolated lesion (2) or in association with a syrinx (1) or lipomyelomeningocele (1). One of these patients had a neurologic deficit detected on careful preoperative evaluation. The other three, two of whom were less than 2 years old, had no detectable deficit. Neither the extent of the anorectal malformation, the absence of associated congenital anomalies, nor the demonstration of normal vertebral anatomy on plain radiographs of the spine precluded the presence of occult spinal dysraphism. Therefore, we recommend that all patients with anorectal anomalies undergo MRI imaging of their spines during initial evaluation to screen for occult spinal dysraphism. In addition, consideration should be given to recalling older patients for MRI evaluation.
More children with CNS tumors will continue to be cured of their neoplasms as a result of improved surgical, radiotherapeutic, and chemotherapeutic intervention. The complex problems seen in these patients mandate their treatment at academic centers actively involved in therapeutic investigations and capable of providing comprehensive multidisciplinary care.